Infectious viral diseases are recognized as an important medical problem and, with the aim of treating such diseases, attempts have been made to develop a drug which has antiviral activity but has no activity to inhibit growth of normal cell lines. For example, extensive studies have been conducted on phosphonate nucleotides as selective antiviral agents. Illustratively, it has been reported that 9-(2-phosphonylmethoxy)ethyladenine (PMEA), 9-(2-phosphonylmethoxy)ethyl-2,6-diaminopurine (PMDAP) and the like compounds are effective against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), human immunodeficiency virus (HIV) and human hepatitis B virus (HBV) (Yokota et al., Antimicrob. Agents Chemother., 35, 394 (1991); Votruba et al., Mol. Pharmacol., 3, 524 (1987)).
However, these known phosphonate nucleotides have a problem in terms of safety such as a possibility of causing toxicity and mutagenicity, typically including bone marrow cell growth inhibition, in the living body (Antiviral Research, 16, 77 (1991)), and, since these compounds do not have oral absorption ability (De Clercq et al., Antimicrob. Agents Chemother., 33, 185 (1989)), their route of administration is limited to intravenous injection, intramuscular injection and the like parenteral administration in order to obtain enough blood levels for exerting their effects. Since the treatment by parenteral administration is difficult to apply to outpatients, such a method is not suitable for the treatment of AIDS, hepatitis B and the like diseases which require long-term therapy.
On the other hand, the inventors of the present invention have previously found that specified ester derivatives of a phosphonate nucleotide show high oral absorption ability (EP 632048), but they have not been put into practical use yet.